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RESEARCH PRODUCT
Cladribine exerts an immunomodulatory effect on human and murine dendritic cells
Felix LuessiValérie JolivelSteffen LerchBettina TrinschekMario HuboHelmut JonuleitLaura Poisa-beiroStefan H.p. KrausMagdalena PaterkaFrauke Zippsubject
Cell SurvivalT-LymphocytesT cellImmunologyBiologyMicePhagocytosismedicineAnimalsHumansImmunologic FactorsImmunology and AllergyCytotoxic T cellAntigen-presenting cellCladribineCells CulturedCell ProliferationPharmacologyCD86ChemotaxisCell DifferentiationDextransDendritic CellsDendritic cellmedicine.diseaseMice Inbred C57BLLeukemiamedicine.anatomical_structureImmunologyLeukocytes MononuclearCancer researchCladribineCytokinesTumor necrosis factor alphaFluorescein-5-isothiocyanatemedicine.drugdescription
Cladribine is a purine nucleoside analog developed to treat lymphoid malignancies. Reported therapeutic benefits for the autoimmune disease multiple sclerosis indicate additional immunomodulatory effects beyond the well-characterized cytotoxic activity causing lymphopenia. Here, we demonstrate that cladribine reduces the secretion of inflammatory cytokines and chemokines by murine and human dendritic cells, the most potent antigen-presenting cells. This compound also modulates the expression of the activation markers CD86 and MHC II. Furthermore, cladribine affects the T cell priming capacity of dendritic cells, resulting in reduced induction of interferon-γ- and tumor necrosis factor-α-producing T cells and increased induction of interleukin-10-producing T cells. These effects, observed at cladribine concentrations in the therapeutically relevant range of serum steady-state concentrations for leukemia and multiple sclerosis, confirm the immunomodulatory activity of cladribine.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-02-01 | International Immunopharmacology |